X-102602392-C-T

Variant names:

• chrX-102602392-C-T
• rs138502487
• NM_001168478.2:c.251C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001168478.2(ARMCX5):​c.251C>T​(p.Thr84Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000917 in 1,210,024 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 49 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.000098 (0 hom. 46 hem.)
• Consequence: ARMCX5 NM_001168478.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.421
• Publications: 0 publications found

Genes affected

ARMCX5 (HGNC:25772): (armadillo repeat containing X-linked 5)

ENSG00000271147 (HGNC:):

ARMCX5-GPRASP2 (HGNC:42000): (ARMCX5-GPRASP2 readthrough) This locus represents naturally occurring readthrough transcription among the adjacent armadillo repeat containing, X-linked 5 (ARMCX5), G protein-coupled receptor associated sorting proteins 1 and 2 (GPRASP1 and GPRASP2), basic helix-loop-helix family member b9 (BHLHB9), and long intergenic non-protein coding RNA 630 (LINC00630) genes on chromosome X. Transcripts may make use of multiple alternative promoters and polyadenylation signals in this region. Readthrough transcripts may produce proteins identical to the proteins encoded by GPRASP2 or BHLHB9. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.053840607).
• BS2: High Hemizygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168478.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMCX5	NM_001168478.2	MANE Select	c.251C>T	p.Thr84Ile	missense	Exon 4 of 4	NP_001161950.1	Q6P1M9
	ARMCX5	NM_001168479.2		c.251C>T	p.Thr84Ile	missense	Exon 6 of 6	NP_001161951.1	Q6P1M9
	ARMCX5	NM_001168480.2		c.251C>T	p.Thr84Ile	missense	Exon 6 of 6	NP_001161952.1	Q6P1M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMCX5	ENST00000473968.7	TSL:2 MANE Select	c.251C>T	p.Thr84Ile	missense	Exon 4 of 4	ENSP00000473737.2	Q6P1M9
	ARMCX5	ENST00000479502.2	TSL:1	c.251C>T	p.Thr84Ile	missense	Exon 3 of 3	ENSP00000474470.2	Q6P1M9
	ENSG00000271147	ENST00000466616.6	TSL:1	n.466+415C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 3 AN: 112074 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000328 AC: 6 AN: 182780 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000738

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000984 AC: 108 AN: 1097950 Hom.: 0 Cov.: 31 AF XY: 0.000127 AC XY: 46 AN XY: 363316

African (AFR) AF: 0.00 AC: 0 AN: 26398

American (AMR) AF: 0.00 AC: 0 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30194

South Asian (SAS) AF: 0.00 AC: 0 AN: 54140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.000114 AC: 96 AN: 841874

Other (OTH) AF: 0.000260 AC: 12 AN: 46090

GnomAD4 genome AF: 0.0000268 AC: 3 AN: 112074 Hom.: 0 Cov.: 23 AF XY: 0.0000876 AC XY: 3 AN XY: 34240

African (AFR) AF: 0.0000325 AC: 1 AN: 30794

American (AMR) AF: 0.00 AC: 0 AN: 10599

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3542

South Asian (SAS) AF: 0.00 AC: 0 AN: 2687

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53211

Other (OTH) AF: 0.00 AC: 0 AN: 1509

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.0
DANN	Benign	0.90
DEOGEN2	Benign	0.027	T
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.42
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.022
Sift	Benign	0.092	T
Sift4G	Benign	0.17	T
Polyphen		0.0010	B
Vest4		0.071
MVP		0.068
MPC		0.13
ClinPred		0.011	T
GERP RS		-0.70
Varity_R		0.055
gMVP		0.17
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs138502487; hg19: chrX-101857320;